Samuel J. Keith

The expert consensus guideline series

Abstract Over the past decade, many new epilepsy treatments have been approved in the United States, promising better quality of life for many with epilepsy. However, clinicians must now choose among a growing number of treatment options and possible combinations. Randomized clinical trials (RCTs) form the basis for evidence-based decision making about best treatment options, but they rarely compare active therapies, making decisions difficult. When medical literature is lacking, expert opinion is helpful, but may contain potential biases. The expert consensus method is a new approach for statistically analyzing pooled opinion to minimize biases inherent in other systems of summarizing expert opinion. We used this method to analyze expert opinion on treatment of three epilepsy syndromes (idiopathic generalized epilepsy, symptomatic localization-related epilepsy, and symptomatic generalized epilepsy) and status epilepticus. For all three syndromes, the experts recommended the same general treatment strategy. As a first step, they recommend monotherapy. If this fails, a second monotherapy should be tried. Following this, the experts are split between additional trials of monotherapy and a combination of two therapies. If this fails, most agree the next step should be additional trials of two therapies, with less agreement as to the next best step after this. One exception to these recommendations is that the experts recommend an evaluation for epilepsy surgery after the third failed step for symptomatic localization-related epilepsies. The results of the expert survey were used to develop user-friendly treatment guidelines concerning overall treatment strategies and choice of specific medications for different syndromes and for status epilepticus.

Effects of chronic haloperidol and clozapine treatments on frontal and caudate neurochemistry in schizophrenia

N-Acetyl-aspartate (NAA), a marker of neuronal integrity, has been found to be reduced in frontal regions in schizophrenia. However, the impact of antipsychotic drug type on NAA has not been carefully evaluated. We studied outpatients with schizophrenia/schizoaffective disorders chronically treated with haloperidol or clozapine and normal controls with single-voxel 1H-MRS of the caudate nuclei and the left frontal lobe. Concentrations of NAA, choline containing compounds (Cho) and creatine plus phosphocreatine (Cre) were determined and corrected for the proportion of cerebrospinal fluid (CSF) in each voxel. The haloperidol-treated group had significantly lower CSF-uncorrected and CSF-corrected left frontal NAA than the normal controls, with the clozapine group having intermediate concentrations. The haloperidol-treated group had significantly lower CSF-uncorrected caudate NAA than the normal controls, but the three groups did not differ after correcting for CSF fraction. Performance times in the Grooved Pegboard, a measure of motor dexterity and proxy for parkinsonism, were correlated with CSF-uncorrected and CSF-corrected left frontal NAA. Demographic and illness-related variables were not related to NAA. Exposure to haloperidol-like drugs may in part account for the frontal NAA reductions previously reported in schizophrenia. Adjustment for proportion of voxel CSF should be considered in 1H-MRS studies.

A critical review of research on psychosocial treatment of schizophrenia

In the following review, the evidence for the effectiveness of the psychosocial treatments of schizophrenia are evaluated. Although most studies focus on relapse and hospitalization, when available, we present information on other domains of outcome (e.g., social adjustment and employment). We begin with family treatments for schizophrenia, then intensive case management, followed by social skills training, supported employment programs, and finally, individual psychotherapy. The topics have been chosen in descending order of available critical supportive studies. Recommendations for specific psychosocial interventions (including target populations) are discussed. Overall psychosocial treatments have been shown to reduce schizophrenic relapses but have not convincingly generalized to improving other facets of the illness. Despite this, psychosocial treatments should be supported and further research to improve them is necessary.

Treatment of Weight Gain with Fluoxetine in Olanzapine-Treated Schizophrenic Outpatients *

Significant weight gain is a side effect associated with olanzapine treatment in some patients. We investigated the efficacy of high-dose fluoxetine as a weight-reducing agent for patients who develop early weight gain with olanzapine treatment. Patients that gained ⩾3% of their baseline weight in the initial 8 weeks of olanzapine treatment (n=31) were randomized to double-blind treatment with placebo or fluoxetine (60 mg/day). Clinical, weight, and weight-related measures were assessed. Fluoxetine failed to demonstrate weight-reducing effects (fluoxetine group: baseline mean 80.5 kg, SD=19.1, last mean=83.5 kg, SD=19.8; placebo group: baseline mean=77.1 kg, SD=12.1, last mean=78.8 kg, SD=10.6; F=1.3; df=1, 18; p=0.3). There were no differential effects in psychopathology, extrapyramidal side effects or weight-related measures between the placebo and fluoxetine groups. Serotonin reuptake inhibitors are probably not a practical option to counteract weight gain induced by atypical antipsychotics. Atypical-induced weight gain may result from mechanisms other than 5HT reuptake blockade.

Schizophrenia: Improving Outcome

Therapeutic advances over the last four decades have enabled most persons with schizophrenia to live in the community. Nevertheless, the majority will continue to experience various symptoms and to have social and cognitive disabilities. With the development of new medications and psychosocial interventions, outpatient status can no longer be viewed as a satisfactory final outcome. This article presents the current state of schizophrenia therapeutics in a variety of clinically relevant situations: first-episode psychosis, treatment-resistant psychosis, chronic, relapsing psychosis, continuous poor functioning, and chronic psychosis not responsive to pharmacotherapy. The first-line atypical antipsychotics should generally be used, mainly because of their comparatively benign side-effect profiles, and they should be given as early as possible in the illness. The clinician should not be quick to accept persistent psychosis; the second-line atypical clozapine should be tried early in the course of the disease in patients showing treatment resistance. For patients residing with their families, educational and supportive family interventions have an important effect on relapse prevention; for those who live on their own and suffer frequent relapses, Assertive Community Treatment may be helpful. Patients with psychosis that is not responsive to pharmacotherapy may benefit from specific modalities of cognitive-behavioral therapy currently being developed, while persons with persistent negative symptoms and limited social competence may find social-skills training useful. In addition, new programs of supported employment may enable some patients to maintain competitive employment.

Ethics in Psychiatric Research

Controversy has arisen in recent years about the participation of psychiatric patients in questionably ethical research protocols. Consequently, academic psychiatrists have been called upon to enrich their understanding of the ethical aspects of research and to teach residents more intensively about these issues in scientific methodology. Toward these ends, the authors have assembled an extensive resource listing in the area of psychiatric research ethics. Articles were identified through MEDLINE and BIOETHICS LINE computerized searches and the authors’ review of relevant literature through 1996. Emphasis was placed on those pieces with special historical value, empirical studies, and papers that provide background on the current controversies in psychiatric research ethics. The references were organized into five logical categories. Based on the resource review, the authors briefly discuss areas related to research ethics that merit greater attention in academic psychiatry.

Maintenance treatment of schizophrenia: a review of dose reduction and family treatment strategies.

Maintenance treatment in schizophrenia requires the integration of both medication and psychosocial treatment interventions for maximum effect. We review the recent evidence for strategies drawn from both domains. For the use of anti-psychotic medication we focus on studies of dose reduction using two strategies that differ in assumptions regarding the action of medication. They are: continuous low-dose and targeted, early intervention or intermittent treatment. For psychosocial interventions we focus on studies of family treatment. Regarding dose reduction, we conclude that both strategies are feasible but the targeted strategy incurs higher relapse and rehospitalization rates. Regarding family treatment, we conclude that family treatment provides benefits beyond other psychosocial interventions or usual care, but that there is no evidence for differences in efficacy among family treatments.

Leadership experiences and characteristics of chairs of academic departments of psychiatry.

ObjectiveEffective leadership in academic medicine requires a broad constellation of skills, experiences, and core values. The authors sought to describe and define these.MethodThe authors conducted a web-based survey among 132 Chairs of North American departments of psychiatry.ResultsEighty-five Chairs (64%) responded to the survey, the majority of whom were first-time Chairs. Identified leadership attributes included strategic/visionary acumen, interpersonal communication skills, core administrative and academic/technical skills, motivational capacity, personal integrity, and altruism/tenacity.ConclusionThe identified values are consistent with the leadership attributes that are described as necessary for success in the business community. Developing the required skillset among faculty who aspire to become a departmental Chair is an important commitment for Deans and extant psychiatry Chairs.

Transition from acute to maintenance treatment: prediction of stabilization.

The stabilization period that follows the exacerbation of a schizophrenic illness represents a critical point in the course of the illness. Successful stabilization is a prerequisite to long-term tenure in the community and the possibility of improvement in functional outcome. In this paper we present an operational definition of stabilization, developed in the context of a study of long-term maintenance treatment that incorporates time, symptomatic equilibrium and consistency of medication dosage. Patients were identified at the time of hospitalization and followed prospectively to determine whether or not they met stabilization criteria. Characteristics that predicted successful stabilization included measures drawn from the domains of patient personal characteristics and psychiatric history, symptoms of psychopathology and side effects in response to initial treatment and family judgments. These patients were treated primarily with fluphenazine decanoate, and five distinct dosing strategies with this agent were identified retrospectively. The dosing strategies distinguished the length of time to subsequent stabilization. The implications of these findings for clinical management of schizophrenia are discussed.

Eberhard H Uhlenhuth.

Eberhard H Uhlenhuth, MD, was a leading investigator in the psychopharmacology of anxiety disorders and is well known globally as an expert in the psychopharmacology of benzodiazepines. He passed away at the age of 88 on 7 June 2016. His research was elegant in its aims and design, and his nearly 200 published papers were clear, incisive, and highly influential. His approach to understanding the scope of these agents was thoughtful and well reasoned, and this characterized his approach to science and his clinical work. Uhli, as he was called, was a terrific colleague and mentor to young faculty. One of us (AFS) got to know him when working on the potential antidepressant properties of benzodiazepines. He was ever so encouraging and helpful to this young academic. The other (SJK) knew him as a generous faculty colleague who, in his later years, always insisted that he had nothing to teach the students, yet continued to receive teacher-of-the-year recognition. He was a modest and giving person. Uhli earned his bachelor’s degree from Yale and his MD from Johns Hopkins. He was elected into Phi Beta Kappa and Alpha Omega Alpha. He did his residency at Hopkins and eventually made his way to the University of Chicago, where he became Professor of Psychiatry. In later years he moved to the University of New Mexico, where he was a Distinguished Professor of Psychiatry. Always willing to help careers, both young and old, his work spanned decades. He served on several editorial boards, including the Archives of General Psychiatry, the Journal of Affective Disorders, and Neuropsychopharmacology. He served on the Scientific Council of the National Institute of Drug Abuse. He was a Founding Fellow of the ACNP from its beginning in 1961, and in 1986 he was President. He loved the College, but in the past few years stopped attending the Annual Meetings. When asked a few years ago about his not attending, he said he thought he would likely not know anyone. I (AFS) indicated that he would know me and that many would know him. We would know him for that wonderful warm personality, twinkle in his eye, terrific sense of humor, and his encyclopedic base of knowledge. We have lost a great man whom we will miss dearly.